title: Real-time amyloid aggregation monitoring with a photonic crystal-based approach.
abstract: We propose the application of a new label-free optical technique based on photonic nanostructures to real-time monitor the amyloid-beta 1-42 (Aβ(1-42)) fibrillization, including the early stages of the aggregation process, which are related to the onset of the Alzheimer's Disease (AD). The aggregation of Aβ peptides into amyloid fibrils has commonly been associated with neuronal death, which culminates in the clinical features of the incurable degenerative AD. Recent studies revealed that cell toxicity is determined by the formation of soluble oligomeric forms of Aβ peptides in the early stages of aggregation. At this phase, classical amyloid detection techniques lack in sensitivity. Upon a chemical passivation of the sensing surface by means of polyethylene glycol, the proposed approach allows an accurate, real-time monitoring of the refractive index variation of the solution, wherein Aβ(1-42) peptides are aggregating. This measurement is directly related to the aggregation state of the peptide throughout oligomerization and subsequent fibrillization. Our findings open new perspectives in the understanding of the dynamics of amyloid formation, and validate this approach as a new and powerful method to screen aggregation at early stages.
authors.affiliation: Optics & Photonics Technology Laboratory, Institute of Microengineering, École Polytechnique Fédérale de Lausanne (EPFL), CH-2000 Neuchâtel (Switzerland); Laboratory of Organic Chemistry, Institute of Chemistry, University of Neuchâtel, CH-2000, Neuchâtel (Switzerland).
authors.forename: Sara
authors.initials: S
authors.lastname: Santi
authors.forename: Valeria
authors.initials: V
authors.lastname: Musi
authors.forename: Emiliano
authors.initials: E
authors.lastname: Descrovi
authors.forename: Vincent
authors.initials: V
authors.lastname: Paeder
authors.forename: Joab
authors.initials: J
authors.lastname: Di Francesco
authors.forename: Lubos
authors.initials: L
authors.lastname: Hvozdara
authors.forename: Peter
authors.initials: P
authors.lastname: van der Wal
authors.forename: Hilal A
authors.initials: HA
authors.lastname: Lashuel
authors.forename: Annalisa
authors.initials: A
authors.lastname: Pastore
authors.forename: Reinhard
authors.initials: R
authors.lastname: Neier
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Herzig
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D015374:Biosensing Techniques; D003460:Crystallization; D046529:Microscopy, Electron, Transmission; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D017785:Photons; D011092:Polyethylene Glycols / Q000737:chemistry; D012031:Refractometry; D013499:Surface Properties
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D011092:Polyethylene Glycols
keywords: Alzheimer’s disease; aggregation; amyloid beta-peptides; biosensing; photonic crystals